ustekinumab (Absimky / DMB 3115 / DA3115)

Clinical Outcomes After Ustekinumab Biosimilar Switching in Crohn's Disease: the USBIOS IG-IBD Study.

Ribaldone Davide Giuseppe DG, Tribocco Elisa E, Scaldaferri Franco F, Murgiano Marco M et al.

Controlled real-world evidence on nonmedical switching from reference ustekinumab to biosimilars in Crohn's disease (CD) is limited. We compared 6-month outcomes after switching versus continued reference treatment. In this prospective observational cohort at 18 Italian centers, adults with CD in clinical remission (Harvey-Bradshaw Index <5), steroid-free for ≥8 months of reference ustekinumab, underwent a procurement-driven switch to 1 of 3 approved biosimilars or continued reference treatment. The expanded clinical-success endpoint required clinical remission without systemic corticosteroids, anti-interleukin-12/23 discontinuation, inflammatory bowel disease-related hospitalization, or intestinal surgery. The protocol-specified noninferiority margin was -15%. Among 462 patients, 337 switched and 125 continued reference ustekinumab; only 4 (0.9%) received every-4-week dosing. Expanded clinical success occurred in 306 of 332 switched patients (92.2%) and 114 of 123 controls (92.7%; risk difference, -0.5%, 95% CI -5.9 to 4.9), meeting the noninferiority criterion. Results were consistent for the protocol-defined three-component composite and after propensity-score weighting. Biosimilar persistence was 93.7%; switch-back occurred in 1.2%. Two adverse events were reported after switching. In clinically stable CD, observed 6-month effectiveness and safety after procurement-driven ustekinumab biosimilar switching were similar to continued reference treatment. Longer-term studies, particularly in patients receiving every-4-week dosing, are needed.

Correction to: Efficacy and safety of ustekinumab biosimilars for treating moderate‑to‑severe plaque psoriasis: a systematic review and network meta‑analysis.

Ye Yingying Y, Liu Chenyu C, Jia Luyao L, Tang Xin X et al.

Risk of Adverse Pregnancy Outcomes in Patients with Non-Communicable, Chronic Inflammatory Barrier Diseases Under Systemic Treatment: A Large-Scale Retrospective Cohort Study.

Brouer Inga Catharina IC, Zani Aida A, Curman Philip P, Ludwig Ralf J RJ et al.

Chronic inflammatory barrier diseases (CIBDs) affect many women of reproductive age, yet the safety of biologics during pregnancy remains inadequately investigated. This retrospective cohort study used the US Collaborative Network of TriNetX to evaluate the risk of adverse pregnancy outcomes (APOs) among women with CIBD receiving tumor necrosis factor inhibitors (TNFis), interleukin-23 inhibitors (IL-23is), or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), compared with untreated CIBD controls and the general pregnant population. Among 1842 pregnant women with CIBD receiving systemic therapy, 1188 were exposed to TNFis, 170 to IL-23is, 370 to azathioprine (csDMARD), and 114 to methotrexate (MTX) (csDMARD). The incidence of any APO ranged from 11% in untreated CIBD controls to 19% with ustekinumab (IL-12/23i). Among treatment groups, rates were 17% with TNFis, 18% with IL-23is, 13% with azathioprine, and 15% with MTX, compared with 17% in the general pregnant population. APO rates were comparable between the overall TNFi group and the TNFi group excluding certolizumab pegol (CZP) (TNFi). In the only non-exploratory comparison, TNFi exposure was associated with higher risks of (pre-)eclampsia and hypertension but a lower risk of abortion or intrauterine death versus CIBD controls, with no significant difference for overall APO. No treatment group showed a markedly increased overall APO risk, supporting tailored decision-making that balances the consequences of uncontrolled maternal disease against individual treatment-associated risks.

Advancing Equity and Patient Partnership in Clinical Trials for Inflammatory Bowel Disease: A Model for Inclusive Trial Design.

Rubin David T DT, Yarur Andres A, Wood Renika R, Chen Brian Po-Han BP et al.

Efficacy rates of advanced therapies for inflammatory bowel disease (IBD) may be improved by combination therapy approaches, which are being investigated in two ongoing phase 4 clinical trials. To ensure relevancy to wider patient populations, understanding and mitigating barriers to recruitment and enrollment early in study development are crucial. Here, we describe the findings of a unique approach in IBD research to proactively engage patients in study design and in the development of accessible patient-facing materials. EXPLORER 2.0 (NCT06045754) and ExiGem (NCT06095128) are phase 4, open-label trials evaluating the efficacy and safety of combination therapy with vedolizumab and either adalimumab or ustekinumab in patients with moderate to severe Crohn's disease (CD), and vedolizumab and tofacitinib in patients with moderate to severe ulcerative colitis (UC). During protocol development, 90-minute interviews were conducted with individuals with CD or UC to gain qualitative insights into patient perceptions on the study design and informed consent forms (ICFs). Interview participants were members of Inspire, a global online health community platform, and not aware of the study sponsor. Overall, participants found the concept of achieving remission with combination therapy appealing, although they expressed concerns about its safety. Other concerns included the stringent eligibility criteria and the number of clinic visits and procedures involved in the trials. Participants were generally positive about the inclusion of patient-reported outcomes. Participants suggested the use of clearer language in patient materials, including ICFs, and the inclusion of a visual dosing timeline to clarify treatment schedules. Using the participants' feedback, the study protocols and ICFs have been amended. These interview findings directly informed patient-centric modifications to trial protocols and patient-facing materials for the EXPLORER 2.0 and ExiGem trials with the essential goal of improving patient diversity and recruitment, which have been suboptimal in IBD research.